Involvement of Rb family proteins, focal adhesion proteins and protein synthesis in senescent morphogenesis induced by hydrogen peroxide

Q. M. Chen, V. C. Tu, J. Catania, M. Burton, O. Toussaint, T. Dilley

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Early passage human diploid fibroblasts develop senescent morphology prematurely within a week after a 2-hour pulse treatment with low or mild dose H2O2. We test here the role of cell cycle checkpoints, cytoskeletal proteins and de novo protein synthesis in senescent morphogenesis following H2O2 treatment. H2O2 treatment causes transient elevation of p53 protein and prolonged inhibition of Rb hyperphosphorylation. Expression of human papillomaviral E6 gene prevented elevation of p53 but did not affect senescent morphogenesis. Expression of human papillomaviral E7 gene reduced the level of Rb protein and prevented induction of senescent morphology by H2O2. The mutants of the E7 gene, in which the Rb family protein binding site was destroyed, could not reduce Rb protein or prevent H2O2 from inducing senescent morphology. Senescent-like cells showed enhanced actin stress fibers. In untreated cells, vinculin and paxillin preferentially distributed along the edge of the cells. In contrast, vinculin and paxillin distributed randomly and sporadically throughout senescent-like cells. E7 expression prevented enhancement of actin filament formation and redistribution of vinculin or paxillin. Neither wild-type nor E7 cells showed changes in the protein level of actin, vinculin or paxillin measured by western blot after H2O2 treatment. Finally, depletion of methionine in the culture medium after H2O2 treatment prevented senescent morphogenesis without affecting dephosphorylation of Rb protein. Our results suggest that senescent morphology likely develops by a program involving activated Rb family proteins, enhancement of actin stress fibers, redistribution of focal adhesion proteins and de novo protein synthesis.

Original languageEnglish (US)
Pages (from-to)4087-4097
Number of pages11
JournalJournal of Cell Science
Volume113
Issue number22
StatePublished - Dec 1 2000

Keywords

  • Cytoskeleton
  • Fibroblast
  • Morphology
  • Senescence
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Cell Biology

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